Research Service, V.A. Medical Center, White River Junction, Vermont, USA.
Mucosal Immunol. 2011 Nov;4(6):671-81. doi: 10.1038/mi.2011.34. Epub 2011 Aug 31.
Knowledge about early innate immune responses at the mucosal surfaces of the female genital tract is important in understanding the pathogenesis of heterosexual transmission of human immunodeficiency virus type-1 (HIV-1). As estradiol decreases inflammatory responses, we postulated that an estradiol-deficient state such as post-menopause could enhance expression of inflammatory factors that stimulate HIV-1 replication. We compare HIV-1 integration, transcription, and viral p24 release levels among ectocervical tissues obtained from pre- and post-menopausal donors. We detected enhanced HIV-1 p24 release levels in post- compared with pre-menopausal tissues (P<0.0001), but saw no difference in HIV-1 integration. Overall, 100% of post-menopausal tissues exhibited levels of HIV-1 transcription above background compared with only 60% of pre-menopausal tissues. Increased HIV-1 transcription was associated with enhanced interleukin (IL)-1β, IL-6, monocyte chemotactic protein-1, growth-regulated oncogene-α, and interferon-γ-inducible protein-10 expression. Neutralization and nuclear factor-κB-targeting small-interfering RNA experiments both decreased HIV-1 transcription, suggesting that the early inflammatory response may facilitate HIV-1 replication in ex vivo ectocervical tissues from post-menopausal women.
了解女性生殖道黏膜表面早期固有免疫反应，对于理解人类免疫缺陷病毒 1 型（HIV-1）异性传播的发病机制很重要。由于雌二醇可降低炎症反应，我们推测，如绝经后等雌二醇缺乏状态可增强刺激 HIV-1 复制的炎症因子表达。我们比较了来自绝经前和绝经后供体的阴道外组织中的 HIV-1 整合、转录和病毒 p24 释放水平。与绝经前组织相比，我们检测到绝经后组织中 HIV-1 p24 释放水平升高（P<0.0001），但 HIV-1 整合无差异。总体而言，与仅 60%的绝经前组织相比，100%的绝经后组织的 HIV-1 转录水平高于背景。HIV-1 转录增加与白细胞介素（IL）-1β、IL-6、单核细胞趋化蛋白-1、生长调节致癌基因-α和干扰素-γ诱导蛋白-10 表达增强有关。中和和核因子-κB 靶向小干扰 RNA 实验均降低了 HIV-1 转录，表明早期炎症反应可能促进绝经后女性阴道外组织中 HIV-1 的复制。
